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CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions

  • Authors:
    • Ru-Chao Jiang
    • Xue-Ying Zheng
    • Sheng-Lan Yang
    • Hai-Jie Shi
    • Jia-Hui Xi
    • Yong-Jian Zou
    • Hua-Qian Dou
    • Yun-Jing Wang
    • Yuan Qin
    • Xiao-Ling Zhang
    • Qing Xiao
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou, Guangdong 511436, P.R. China, Department of Neonatology, Maternal and Children Hospital of Guangdong Province, Guangzhou, Guangdong 510260, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 5
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    Published online on: November 4, 2021
       https://doi.org/10.3892/mmr.2021.12521
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Abstract

Modulating the biological status of endothelial progenitor cells (EPCs), such as function and survival, is essential for therapeutic angiogenesis in ischemic vascular disease environments. This study aimed to explore the role and molecular mechanisms underlying Netrin‑1 in the viability and angiogenic function of EPCs. EPCs were isolated from the bone barrow of adult C57/BL6 mice. The apoptosis and various functions of EPCs were analyzed in vitro by manipulating the expression of Netrin‑1. The TUNEL assay was performed to detect apoptotic EPCs. Cell migration and tube formation assays were performed to detect EPC function. Trypan blue staining was performed to detect cell viability. Western blot analysis was performed to detect the protein expression levels of Netrin‑1, CD146 and apoptotic factors. Quantitative PCR analysis was performed to detect the expression levels of Netrin‑1 receptors. The results demonstrated that treatment with exogenous Netrin‑1 promoted EPC migration and tube formation, whereas transfection with small interfering (si)RNA targeting Netrin‑1 exhibited the opposite effects. Exogenous Netrin‑1 protected EPCs from hypoxia‑induced apoptosis, whereas the interruption of endogenous Netrin‑1 enhancement under hypoxia by Netrin‑1‑siRNA exacerbated the apoptosis of EPCs. Furthermore, CD146, one of the immunoglobulin receptors activated by Netrin‑1, was screened for in the present study. Results demonstrated that CD146 did not participate in Netrin‑1‑promoted EPC function, but mediated the anti‑apoptotic effects of Netrin‑1 in EPCs. In conclusion, Netrin‑1 enhanced the angiogenic function of EPCs and alleviated hypoxia‑induced apoptosis, which was mediated by CD146. This biological function of Netrin‑1 may provide a potential therapeutic option to promote EPCs for the treatment of ischemic vascular diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang R, Zheng X, Yang S, Shi H, Xi J, Zou Y, Dou H, Wang Y, Qin Y, Zhang X, Zhang X, et al: CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions. Mol Med Rep 25: 5, 2022.
APA
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y. ... Xiao, Q. (2022). CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions. Molecular Medicine Reports, 25, 5. https://doi.org/10.3892/mmr.2021.12521
MLA
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y., Dou, H., Wang, Y., Qin, Y., Zhang, X., Xiao, Q."CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions". Molecular Medicine Reports 25.1 (2022): 5.
Chicago
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y., Dou, H., Wang, Y., Qin, Y., Zhang, X., Xiao, Q."CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions". Molecular Medicine Reports 25, no. 1 (2022): 5. https://doi.org/10.3892/mmr.2021.12521
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang R, Zheng X, Yang S, Shi H, Xi J, Zou Y, Dou H, Wang Y, Qin Y, Zhang X, Zhang X, et al: CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions. Mol Med Rep 25: 5, 2022.
APA
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y. ... Xiao, Q. (2022). CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions. Molecular Medicine Reports, 25, 5. https://doi.org/10.3892/mmr.2021.12521
MLA
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y., Dou, H., Wang, Y., Qin, Y., Zhang, X., Xiao, Q."CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions". Molecular Medicine Reports 25.1 (2022): 5.
Chicago
Jiang, R., Zheng, X., Yang, S., Shi, H., Xi, J., Zou, Y., Dou, H., Wang, Y., Qin, Y., Zhang, X., Xiao, Q."CD146 mediates the anti-apoptotic role of Netrin-1 in endothelial progenitor cells under hypoxic conditions". Molecular Medicine Reports 25, no. 1 (2022): 5. https://doi.org/10.3892/mmr.2021.12521
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